Cholecystokinin stimulates a specific ribosomal S6 kinase in rat pancreatic acini.
Stimulation of intact rat pancreatic acini with cholecystokinin (CCK) enhances the phosphorylation of the ribosomal protein S6 in a dose-dependent manner with half maximal stimulation at 40 pM and maximal stimulation at 1 nM CCK octapeptide. Soluble cellular extracts contained S6 kinase activity assayed using purified rat pancreatic ribosomes as substrate. Stimulation by CCK of S6 kinase was concentration dependent, being half maximal at 50 pM and maximal at 1 nM CCK. The phorbol ester 12-O-tetradecanoyl-phorbol 13-acetate (TPA), an activator of protein kinase C, also increased both S6 phosphorylation in intact acini and soluble S6 kinase activity. In order to determine whether S6 kinase mediated S6 phosphorylation following CCK treatment of acini, two-dimensional phosphopeptide analysis was performed for S6 proteins phosphorylated under various conditions. These data suggest that a specific soluble S6 kinase, the activation of which appears to be directly or indirectly mediated by protein kinase C, is the functional enzyme in intact acini that mediates the action of CCK to increase S6 phosphorylation and may be involved in increased protein synthesis in pancreatic acini treated with CCK.
Sung
C K
CK
Department of Physiology, University of California, San Francisco.
Williams
J A
JA
D000818:Animals; D002766:Cholecystokinin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects*; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology*; D010449:Peptide Mapping; D010766:Phosphorylation / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D038601:Ribosomal Protein S6; D019893:Ribosomal Protein S6 Kinases; D012269:Ribosomal Proteins / Q000378:metabolism; D013997:Time Factors
D038601:Ribosomal Protein S6; D012269:Ribosomal Proteins; D002766:Cholecystokinin; D011494:Protein Kinases; D019893:Ribosomal Protein S6 Kinases